Approaches to define the role of SF-1 at different levels of the hypothalamic-pituitary-steroidogenic organ axis

Targeted gene disruption has produced knockout mice lacking the orphan nucl ear receptor steroidogenic Factor 1 (SF-1). These SF-l knockout mice lacked adrenal glands and gonads, resulting in adrenocortical insufficiency and s ex reversal of their internal and external genitalia. They also had impaire d expression of pituitary gonadotropins and agenesis of the ventromedial hy pothalamic nucleus (VMH), confirming roles of SF-I at multiple levels of th e hypothalamic-pituitary-steroidogenic tissue axis. Using the Cre-loxP syst em- we now have generated mice in which SF-1 is inactivated selectively in the anterior pituitary;. These pituitary-specific SF-I knockout mice were s terile and failed to exhibit sexual maturation. Histologically. their gonad s were markedly hypoplastic, weighing only similar to 5% of the gonads of w ild-type mice. Consistent with an important role of SF-1 in gonadotropes. t here were no cells in the pituitary gland that expressed either follicle-st imulating hormone (FSH) or luteinizing hormone (LH), These pituitary-specif ic SF-I knockout mice are a novel genetic model of hypogonadotropic hypogon adism and establish essential roles of SF-1 in gonadotropin expression. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.